DRUG RELEASE PROFILES IN THE SHRINKING PROCESS OF THERMORESPONSIVE POLY(N-ISOPROPYLACRYLAMIDE-CO-ALKYL METHACRYLATE) GELS

Thermoresponsive poly(N-isopropylacrylamide-co-alkyl methacrylate) gels are capable of "on-off" regulation of drug release in response to external temperature changes because a gel surface skin formed with increasing temperature stops drug release from the gel interior. In this gel shrinking process, observation of bubble formation on the surface indicates that pressure is induced within the gel. This pressure may result in an outward convection of water. Drug must therefore be released not only by diffusion but also by convective transport. We have created a drug release model for this shrinking process using a tortuous pore model and simulated four decreasing patterns of release rate for different induction patterns of pressure. Experiments using indomethacin could match simulated release patterns by changing the chemical structure of polymer and thermal gradient. These changes induce different pressure fluctuations within gels and affect the release pattern from the gel "on" state to the "off" state.